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Juvenile Onset Stills Disease

Systemic Juvenile Idiopathic Arthritis

Juvenile onset Stills disease, also referred as systemic-onset juvenile idiopathic arthritis (SoJIA), occurs due to overstimulation of various proinflammatory cytokines, most important being IL-1, IL-6 and TNF-α. It is distinguished from other forms of JIA by extra-articular symptoms such as fever, hepatosplenomegaly, lymphadenopathy and serositis. The diagnosis is made by clinical criteria. IL-1 and IL-6 antagonists, anakira and tocilizumab, are now becoming the mainstay of therapy.

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Presentation

Patients with juvenile onset Stills disease develop both systemic and visceral symptoms. Fever spikes that appear on an almost daily basis is seen in practically all patients [1]. Arthralgia, involving one, but more frequently two or more joints, is the most frequent finding after fever, usually involving the knee, wrist and ankle [7]. Synovial cysts are also a frequent finding in these patients, while additional complaints include a macular rash, serositis (either pericarditis or pleuritis), generalized lymphadenopathy and hepatosplenomegaly [3] [5]. Symptoms tend to be more pronounced during fever spikes and may be completely absent once the fever has resolved [3], which might be of great help in the diagnostic workup.

Splenomegaly
  • […] fever with spike in the evening) persisting for a minimum of 15 days, with at least one of the following manifestations: skin rash (evanescent, non-fixed erythematous rash that accompanies fever spikes), generalized lymphadenopathy, hepatomegaly and/or splenomegaly[stillsdisease.org]
  • Juvenile onset Stills disease, also commonly described in literature as systemic-onset juvenile idiopathic arthritis (SoJIA), was initially established at the end of the 19th century when fever, arthritis, splenomegaly and lymphadenopathy were observed[symptoma.com]
  • Lymphadenopathy, splenomegaly, hepatomegaly, and sore throat are also common. Pericarditis, pleuritis, pericardial effusion and pleural effusion may occur but is less likely. They present as underlying complications. 8.[slideshare.net]
  • Minor criteria may include sore throat, lymphadenopathy, negative rheumatoid factor, abnormal liver function tests, hepatomegaly or splenomegaly. Five criteria are needed for diagnosis with at least two of them being major.[press.mu-varna.bg]
  • Other prominent manifestations (seen in 50% of patients) include myalgias, carpal ankylosis, weight loss ( 10% body weight), lymphadenopathy, hepatomegaly, splenomegaly, pleuritis and pericarditis.[rheumaknowledgy.com]
Generalized Lymphadenopathy
  • Appearance of rash, hepatosplenomegaly, serositis and generalized lymphadenopathy.[symptoma.com]
  • lymphadenopathy, hepatomegaly and/or splenomegaly, or serositis (pleuritis or pericarditis).[stillsdisease.org]
  • It differs from classical rheumatoid arthritis in that it is more often marked by acute febrile onset, and generalized lymphadenopathy and hepatosplenomegaly are more prominent.[icd10data.com]
  • Leukemia/lymphoma patients also have fever, rash and generalized lymphadenopathy. The differentiating features are the low-grade fever, severe bone and joint pain mainly at night, and abnormal cell counts though leaning towards pancytopenia.[clinicaladvisor.com]
Fever
  • Symptoms tend to be more pronounced during fever spikes and may be completely absent once the fever has resolved, which might be of great help in the diagnostic workup.[symptoma.com]
  • Still's Disease Symptoms Fever Fever is part of the body's own disease-fighting arsenal. Rising body temperatures apparently are capable of killing off many disease-producing organisms. For that reason, low fevers should normally go untreated.[medicinenet.com]
  • The clinical signs include fever with oscillating temperatures over a 24-hour period and peaks of over 39 C or more. These fever peaks are associated with transient cutaneous eruptions and diffuse erythematosis or urticarial-like lesions.[orpha.net]
  • Fever can occur at the same time every day or twice a day (often in late afternoon or evening) with a spontaneous rapid return to baseline (vs. septic arthritis of continuous fever). The rash often occurs with fever.[en.wikipedia.org]
  • Systemic symptoms often start with daily high fevers, often presenting every afternoon or evening for a few weeks, and accompanied by the salmon-pink rash over the body.[autoinflammatory.org]
Pain
  • Of all patients with Still's disease, 100% have high intermittent fever, and 100% have joint inflammation and pain, muscle pain with fevers, and develop persistent chronic arthritis.[medicinenet.com]
  • Until the introduction of novel immunomodulating agents, NSAIDs and corticosteroids were the mainstay of managing symptoms such as fever, rash and joint pain.[symptoma.com]
  • This causes excessive pain and swelling, resulting in bone erosion and joint deformity. Children, who develop JRA often experience fatigue, stiffness, and some joint pain.[dovemed.com]
  • Visceral complications (pericarditis, pleural effusion or serous peritonitis with abdominal pain) may be present.[orpha.net]
  • People with Systemic Juvenile Idiopathic Arthritis (SJIA) (also known as Stills) can have recurrent fevers, a macular rash, joint pain, joint deformities, an enlarged liver and/or spleen, and can occasionally have polyserositis, lung involvement or pericardial[autoinflammatory.org]
Lymphadenopathy
  • Appearance of rash, hepatosplenomegaly, serositis and generalized lymphadenopathy.[symptoma.com]
  • MAS is a severe, potentially life-threatening disorder, and clinically characterized by fever, hepatosplenomegaly, lymphadenopathy, neurologic dysfunction, and coagulopathy.[stillsdisease.org]
  • Systemic JIA may have internal organ involvement such as hepatosplenomegaly, lymphadenopathy, serositis, hepatitis, or tenosynovitis. [ citation needed ] A polymorphism in macrophage migration inhibitory factor has been associated with this condition.[en.wikipedia.org]
  • Lymphadenopathy, splenomegaly, hepatomegaly, and sore throat are also common. Pericarditis, pleuritis, pericardial effusion and pleural effusion may occur but is less likely. They present as underlying complications. 8.[slideshare.net]
  • Classical Presentation: Fever, salmon-colored rash, lymphadenopathy, myalgias, FERRITIN... ev negative ---------------- Juvenile idiopathic Arthritis, which has 3 forms 1) Pauciarticular few joints 2) Poliarticular many joints 3) Systemic Still's Disease[usmleforum.com]
Fatigue
  • Children, who develop JRA often experience fatigue, stiffness, and some joint pain. There are seven types of Juvenile Rheumatoid Arthritis: Systemic Juvenile Idiopathic Arthritis: This type of arthritis affects the child’s entire body.[dovemed.com]
  • Extreme fatigue can accompany waves of high fevers that rise daily to 102 F (39 C) or even higher and rapidly return to normal levels or below. Fever spikes often occur at approximately the same time every day.[medicinenet.com]
  • Extreme fatigue can accompany waves of high fevers that rise daily to 102 degrees F (39 degrees C) or even higher and rapidly return to normal levels or below. Fever spikes often occur at nearly the same time every day.[checkorphan.org]
  • AOSD is classified as an inflammatory illness that often causes fatigue and swelling in joints, tissues, organs, and lymph nodes.[healthline.com]
  • Extreme fatigue can accompany waves of high fevers that rise to 104 degrees F (41 degrees C) or even higher and can rapidly return to normal levels or below.[stillsdisease.org]
Weight Loss
  • Poor appetite, nausea , and weight loss are common. There is also commonly swelling of the lymph glands, enlargement of the spleen and liver, and sore throat .[medicinenet.com]
  • Poor appetite, nausea, and weight loss are common. There is also commonly swelling of the lymph glands, enlargement of the spleen and liver, and sore throat.[checkorphan.org]
  • Other symptoms of AOSD include: sore throat swollen and tender joints inflamed or swollen lymph nodes muscle pain abdominal pain pain associated with deep breathing weight loss In some extreme cases, individuals develop an enlarged liver or spleen.[healthline.com]
  • Frequently a dramatic drop in serum albumin will parallel a dramatic drop in hematocrit and weight loss.[rheumaknowledgy.com]
  • May be associated with weight loss or family history. Malignancy: Night pain, weight loss, easy bruising can all be features. Leukaemia, lymphoma, neuroblastoma, Ewing's sarcoma, bony tumours.[patient.info]
Pleural Effusion
  • Visceral complications (pericarditis, pleural effusion or serous peritonitis with abdominal pain) may be present.[orpha.net]
  • Some patients develop inflammation around the heart (pericarditis) and lungs (pleuritis), with occasional fluid accumulation around heart ( pericardial effusion ) and lungs ( pleural effusion ).[medicinenet.com]
  • Cervical spine radiographs may demonstrate: atlantoaxial subluxation odontoid erosions ankylosis, especially of the facet joints Hepatosplenomegaly may be seen on abdominal radiographs, and pericardial or pleural effusions may be seen on chest radiographs[radiopaedia.org]
  • Some patients develop inflammation around the heart (pericarditis) and lungs (pleuritis), with occasional fluid accumulation around heart (pericardial effusion) and lungs (pleural effusion).[checkorphan.org]
  • Other complications may include: Arthritis in several joints Liver disease Pericarditis Pleural effusion Spleen enlargement Call your provider if you have symptoms of AOSD.[medlineplus.gov]
Nausea
  • Poor appetite, nausea , and weight loss are common. There is also commonly swelling of the lymph glands, enlargement of the spleen and liver, and sore throat .[medicinenet.com]
  • Poor appetite, nausea, and weight loss are common. There is also commonly swelling of the lymph glands, enlargement of the spleen and liver, and sore throat.[checkorphan.org]
  • […] inflammation Faint, salmon-coloured rash, which may be bumpy or flat and will often occur with fever Muscle pain, which often comes and goes with fever and may be severe Sore throat Swollen lymph nodes in the neck Enlarged liver and/or spleen Poor appetite, nausea[jointhealth.org]
  • Poor appetite, nausea, and weight loss may occur. Lymphadenopathy, splenomegaly, hepatomegaly, and sore throat are also common. Pericarditis, pleuritis, pericardial effusion and pleural effusion may occur but is less likely.[slideshare.net]
Hepatomegaly
  • […] typically daily high fever with spike in the evening) persisting for a minimum of 15 days, with at least one of the following manifestations: skin rash (evanescent, non-fixed erythematous rash that accompanies fever spikes), generalized lymphadenopathy, hepatomegaly[stillsdisease.org]
  • Lymphadenopathy, splenomegaly, hepatomegaly, and sore throat are also common. Pericarditis, pleuritis, pericardial effusion and pleural effusion may occur but is less likely. They present as underlying complications. 8.[slideshare.net]
  • Minor criteria may include sore throat, lymphadenopathy, negative rheumatoid factor, abnormal liver function tests, hepatomegaly or splenomegaly. Five criteria are needed for diagnosis with at least two of them being major.[press.mu-varna.bg]
  • […] diagnostic criteria. [6] Major criteria Minor criteria Fever of at least 39 C for at least one week Sore throat Arthralgias or arthritis for at least two weeks Lymphadenopathy Nonpruritic salmon-colored rash (usually over trunk or extremities while febrile) Hepatomegaly[checkrare.com]
  • […] diagnostic criteria. [7] Major criteria Minor criteria Fever of at least 39 C for at least one week Sore throat Arthralgias or arthritis for at least two weeks Lymphadenopathy Nonpruritic salmon-colored rash (usually over trunk or extremities while febrile) Hepatomegaly[en.wikipedia.org]
Hepatosplenomegaly
  • Appearance of rash, hepatosplenomegaly, serositis and generalized lymphadenopathy.[symptoma.com]
  • In the absence of cutaneous eruptions, the presence of an adenopathy, hepatosplenomegaly or serous effusion also confirm the diagnosis. There is no specific biological sign.[orpha.net]
  • MAS is a severe, potentially life-threatening disorder, and clinically characterized by fever, hepatosplenomegaly, lymphadenopathy, neurologic dysfunction, and coagulopathy.[stillsdisease.org]
  • Migratory salmon colored light pink rash involving the trunk and/or extremities and hepatosplenomegaly are also frequently observed in patients with systemic onset.[radiopaedia.org]
  • Systemic JIA may have internal organ involvement such as hepatosplenomegaly, lymphadenopathy, serositis, hepatitis, or tenosynovitis. [ citation needed ] A polymorphism in macrophage migration inhibitory factor has been associated with this condition.[en.wikipedia.org]
Eruptions
  • In the absence of cutaneous eruptions, the presence of an adenopathy, hepatosplenomegaly or serous effusion also confirm the diagnosis. There is no specific biological sign.[orpha.net]
  • DRESS syndrome has an extremely distinctive skin eruption associated with systemic signs after prolonged use of certain drugs (Figure 3).[clinicaladvisor.com]
Arthritis
  • Arthritis: This type of arthritis does not seem to be associated with any of the other types of arthritis categories, or it may fit into multiple categories.[dovemed.com]
  • Idiopathic Arthritis (Still Disease) - Pipeline by Novartis AG, H1 2016 Systemic-Onset Juvenile Idiopathic Arthritis (Still Disease) - Pipeline by Oncobiologics, Inc., H1 2016 Systemic-Onset Juvenile Idiopathic Arthritis (Still Disease) - Pipeline by[gii.co.jp]
  • […] juvenile idiopathic arthritis (JIA) with extra-articular manifestations like fever and rash apart from arthritis.[en.wikipedia.org]
  • Persistent arthritis (arthritis lasting at least six weeks) is required to make a firm diagnosis of Still's disease. Other diseases (especially infections, cancers, and other types of arthritis) must be excluded.[medicinenet.com]
  • Exclusion criteria are the presence of systemic arthritis or psoriasis in the patient, or a family history of psoriasis in one of the parents or a first-degree relative, HLA B27-positivity in males with onset of arthritis after 6 years of age and detection[orpha.net]
Arthralgia
  • Arthralgia, involving one, but more frequently two or more joints, is the most frequent finding after fever, usually involving the knee, wrist and ankle.[symptoma.com]
  • Major criteria include high spiking fevers 38.5 C, arthralgia or arthritis, a transient, nonpruritic salmon-colored rash and leukocytosis.[press.mu-varna.bg]
  • Major Criteria Fever of 39 C for 1 week Leukocytosis 10,000/microL with 80% polymononuclear leukocytes (predominating granulocytes) Salmon colored rash (usually over the trunk or extremities, non-pruritic) Arthralgia and/or Arthritis 2 week Minor Criteria[slideshare.net]
  • He complained of headache, sore throat, and symmetric arthralgia of the shoulders and knees. Physical examination showed a salmon-colored macular rash on his abdomen and chest.[archivesofrheumatology.org]
  • Salmon rash of Adult JRA Arthritis Arthralgias, arthritis and myositis are universal features of adult JRA though often are preceded by fever by a few weeks.[clinicaladvisor.com]
Joint Swelling
  • It causes joint swelling, pain, stiffness, and loss of motion. It can affect any joint, but is more common in the knees, hands, and feet. In some cases it can affect internal organs as well.[icdlist.com]
  • Arthritis, with joint swelling, often occurs after rash and fevers have been present for some time.[medicinenet.com]
  • Corticosteroids, such as prednisone may be used to control high fever spikes, severe joint swelling and pain, and complications with internal organs.[jointhealth.org]
Myalgia
  • Classical Presentation: Fever, salmon-colored rash, lymphadenopathy, myalgias, FERRITIN... ev negative ---------------- Juvenile idiopathic Arthritis, which has 3 forms 1) Pauciarticular few joints 2) Poliarticular many joints 3) Systemic Still's Disease[usmleforum.com]
  • […] often shows up on the limbs and trunk, and that comes and goes — often along with a fever Joint pain and swelling in any joint, frequently in the knees, ankles, wrists (in adults), and the cervical spine joints (in children) Generalized muscle pain (myalgia[everydayhealth.com]
  • Other prominent manifestations (seen in 50% of patients) include myalgias, carpal ankylosis, weight loss ( 10% body weight), lymphadenopathy, hepatomegaly, splenomegaly, pleuritis and pericarditis.[rheumaknowledgy.com]
  • History Part I: Pattern Recognition: The classic presentation of adult JRA is daily high fevers accompanied by an evanescent salmon colored rash on the trunk along with myalgias and polyarticular arthritis.[clinicaladvisor.com]
Morning Stiffness
  • Often, people with the condition have morning stiffness of joints that lasts for several hours. The fever comes on quickly once per day, most commonly in the afternoon or evening.[medlineplus.gov]
  • In contrast, adult JRA has high spiking fevers, mild arthritis with morning stiffness, and leukocytosis as well as thrombocytosis.[clinicaladvisor.com]
Kidney Failure
  • Amyloidosis can result in kidney failure, while macrophage activation syndrome is characterized by severe onset of liver damage, neurological deficits and further aggravation of existing symptoms.[symptoma.com]

Workup

The diagnosis rests on clinical grounds and proposed criteria include [1]:

From these facts, it can be concluded that a thorough physical examination and carefully obtained patient history are vital parts of the diagnostic workup. Laboratory studies may reveal leukocytosis and elevation of acute-phase reactants - CRP, ESR and fibrinogen [3].

Pericardial Effusion
  • Some patients develop inflammation around the heart (pericarditis) and lungs (pleuritis), with occasional fluid accumulation around heart ( pericardial effusion ) and lungs ( pleural effusion ).[medicinenet.com]
  • Some patients develop inflammation around the heart (pericarditis) and lungs (pleuritis), with occasional fluid accumulation around heart (pericardial effusion) and lungs (pleural effusion).[checkorphan.org]
Elevated Sedimentation Rate
  • The most common laboratory abnormalities include: -greatly elevated sedimentation rate -leukocytosis (in most cases between 15,000-30,000, mainly neutrophiles) -thrombocytosis 400,000 -elevated ferritin levels.[flipper.diff.org]
Synovial Cyst
  • Synovial cysts are also a frequent finding in these patients, while additional complaints include a macular rash, serositis (either pericarditis or pleuritis), generalized lymphadenopathy and hepatosplenomegaly.[symptoma.com]
Pleural Effusion
  • Visceral complications (pericarditis, pleural effusion or serous peritonitis with abdominal pain) may be present.[orpha.net]
  • Some patients develop inflammation around the heart (pericarditis) and lungs (pleuritis), with occasional fluid accumulation around heart ( pericardial effusion ) and lungs ( pleural effusion ).[medicinenet.com]
  • Cervical spine radiographs may demonstrate: atlantoaxial subluxation odontoid erosions ankylosis, especially of the facet joints Hepatosplenomegaly may be seen on abdominal radiographs, and pericardial or pleural effusions may be seen on chest radiographs[radiopaedia.org]
  • Some patients develop inflammation around the heart (pericarditis) and lungs (pleuritis), with occasional fluid accumulation around heart (pericardial effusion) and lungs (pleural effusion).[checkorphan.org]
  • Other complications may include: Arthritis in several joints Liver disease Pericarditis Pleural effusion Spleen enlargement Call your provider if you have symptoms of AOSD.[medlineplus.gov]

Treatment

Until the introduction of novel immunomodulating agents, NSAIDs and corticosteroids were the mainstay of managing symptoms such as fever, rash and joint pain [9]. Because of their long-term use and severe adverse effects over time, however, methotrexate and recently approved IL-1 and IL-6 antagonists have dramatically improved the course and outcome of patients suffering from juvenile onset Stills disease. Although glucocorticoids are still considered as a valuable option, anakira (IL-1 antagonist) and tocilizumab (IL-6 antagonist) have shown much better results and are becoming the foundation of patient management [10]. Tocilizumab may be even combined with methotrexate, but clinical trials still need to prove its safety and efficacy in infants and young children [11].

Prognosis

The prognosis of patients is variable. Approximately 50% of individuals will enter complete remission with appropriate therapy, but the remaining 50% will develop life-long, progressive symptoms that may be severely debilitating [9]. Amyloidosis and macrophage activation syndrome (MAS) are two important and potentially life-threatening complications. Amyloidosis is seen in approximately 5-15% of patients, depending on the geographical regions, and may lead to end-stage kidney disease, with 10-year survival rates established to be around 75% [1]. MAC is an even more serious complication, characterized by overt activation of macrophages and development of severe liver disease, neurological deficits and aggravation of existing symptoms [3]. The appearance of both conditions almost solely depend on the effectiveness of treatment, illustrating the importance of an early diagnosis and appropriate management.

Etiology

Contrary to all other forms of juvenile idiopathic arthritis, in which mutations of HLA genes are responsible for the development of symptoms, the presumed etiological model includes abnormalities of genes and gene products that induce upregulation of various pro-inflammatory cytokines, mainly IL-1, IL-6, TNF-α and MIF [3]. A myriad of additional cytokines, such as IL-4, IL-10, IL-18, as well as myeloid-related protein 8 and 14 (MRP) have been associated with juvenile onset Stills disease [1], but further studies are required to solidify their roles. The exact reason why these molecules activated and why does dysregulation of genes responsible for their activation occurs, however, remains a mystery.

Epidemiology

SoJIA constitutes approximately 10-30% of all JIA cases and its prevalence rates are estimated around 3.5 per 100 000 individuals [1]. Incidence rates vary between 0.4-0.9 per 100,000 individuals across different studies [1] [7]. Despite the fact that young age is a prerequisite for classification of patients into this category of JIA (< 16 years), several studies have shown that the majority of individuals present within their first 5 years of life [1]. Unlike in other forms of JIA, where significant predilection toward females is observed, gender distribution is equal when it comes to juvenile onset Stills disease [3].

Sex distribution
Age distribution

Pathophysiology

The pathogenesis of juvenile onset Stills disease starts with dysregulation and polymorphism of genes that are responsible for regulation of cytokine production. IL-1, IL-6 and TNF-α are the principal pro-inflammatory molecules that have their established roles in the development of this disease. IL-1 is one of the most potent mobilizers of the cells of the immune system, while concentrations of IL-6 and the course of symptoms are shown to be in strong correlation by several studies [4]. When activated, these cytokines cause numerous harmful effects in the human body, including osteopenia as a result of enhanced osteoclastic activity by IL-6, thrombocytosis, leukocytosis and stimulation of acute-phase reactants such as C-reactive protein, fibrinogen and erythrocyte sedimentation rate (ESR) [1] [5]. The role of nuclear factor kappa b (NF-κB) and RANK ligand in the systemic forms of JIA is yet to be determined, but their roles in induction of osteoporosis have been well documented [8]. As a result of cumulative cytokine production and their activation, systemic and visceral symptoms appear.

Prevention

Preventive measures currently do not exist and the focus remains on long-term follow-up and prevention of complications that may arise from juvenile onset Stills disease. Timely treatment and appropriate management through regular check-ups is mandatory in ensuring a good quality of life.

Summary

Juvenile onset Stills disease, also commonly described in literature as systemic-onset juvenile idiopathic arthritis (SoJIA), was initially established at the end of the 19th century when fever, arthritis, splenomegaly and lymphadenopathy were observed in young children by Sir George Frederick Still [1]. Today, together with six other variants, it is one of the forms of juvenile idiopathic arthritis (JIA) and comprises approximately 10-30% of all JIA cases [2]. The appearance of symptoms before 16 years of age distinguishes it from adult-onset Stills disease and the majority of patients present before 5 years of age [1]. Prevalence rates range from 0.4-0.6 per 100,000 individuals across different studies. Gender predilection toward females, which is seen in all JIA subtypes, is not evident in juvenile onset Stills disease and equal distribution among sexes is observed [1]. Although virtually all subtypes of JIA are thought to include mutations of the human leukocytic antigen (HLA), juvenile onset Stills disease stems from altered expression or mutation of genes that code for various pro-inflammatory cytokines such as interleukin-1 (IL-1), IL-6, tumor necrosis factor alpha (TNF-α) and macrophage migration inhibitory factor (MIF) [3]. In fact, IL-6 has shown to be the most important cytokine in the pathogenesis, as its levels directly correlate with the onset and resolution of disease manifestations [4]. As a result of their increased activity, the appearance of spiking fever, hepatosplenomegaly, rash and lymphadenopathy are considered as hallmarks [5]. Pericarditis or pleuritis are frequently observed in these patients as well [3]. Clinical criteria that include polyarticular pain, daily spiking fever for more than two weeks and several exclusion criteria (history of psoriasis, presence of HLA-B27 mutations and other autoimmune diseases and normal serum values of rheumatoid factor) are used to confirm the diagnosis of juvenile onset Stills disease [1]. The use of corticosteroids, methotrexate and non-steroidal anti-inflammatory drugs (NSAIDs) have been listed as potential treatment modalities, but the introduction of IL-1 and IL-6 antagonists into medical practice has drastically improved patient outcomes [6]. Anakira and tocilizumab, respectively, are recently approved immunomodulating drugs that show superior results to other regimens and provide significantly lower rates of adverse effects. The prognosis of juvenile onset Stills disease is variable, ranging from complete remission to development of complications such as amyloidosis and macrophage activation syndrome (MAS), both being severe and even life-threatening [1]. For these reasons, close monitoring and long-term follow-up of patients with this condition is necessary in order to enable an adequate quality of life, but an early diagnosis is equally important.

Patient Information

Juvenile onset Stills disease was initially discovered more than 100 years ago and today it is more commonly known as systemic-onset juvenile idiopathic arthritis, a condition characterized by severe inflammatory changes in the body as a result of genetic mutations and alterations. Namely, mutations and upregulation of genes that regulate production of molecules such as interleukin 1 and 6, which cause significant inflammation and appearance of symptoms such as fever, joint pain, rash and several other. The exact cause of these mutations is not known and symptoms most frequently start before 5 years of age. Juvenile onset Stills disease develops in less than 1 per 100,000 individuals and genders are equally affected. In addition to fever and joint pain, which are the two most important manifestations, enlargement of liver and spleen (hepatosplenomegaly) is a frequent findings, as is lymph node enlargement, rash, pericarditis and pleuritis. Fever appears almost every day and has shown to aggravate symptoms that may become severely debilitating. Moreover, 50% of patients develop a chronic, progressive course of disease that may lead to complications such as amyloidosis and macrophage activation syndrome, with both being potentially fatal. Amyloidosis can result in kidney failure, while macrophage activation syndrome is characterized by severe onset of liver damage, neurological deficits and further aggravation of existing symptoms. A properly obtained patient history and a thorough physical examination can provide all the information necessary to make a presumptive diagnosis. Laboratory findings may reveal increased white blood cell count and markers of inflammation such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and fibrinogen, but there is no direct test to confirm the disease. Treatment principles are focused on alleviating symptoms through administration of drugs that suppress inflammation, such as corticosteroids and non-steroidal anti-inflammatory drugs, but recent introduction of a newer class of drugs that directly inhibit production of cytokines and other pro-inflammatory molecules has revolutionized the management of patients suffering from this condition. Anakira and tocilizumab are interleukin 1 and 6 antagonists, respectively, and their efficacy is superior to all other drugs, but more importantly, adverse effects are minimal compared to other drugs that are used. Overall prognosis is good with long-term follow-up and therapy, but an early diagnosis is necessary to prevent complications and ensure a good quality of life.

References

Article

  1. Gurion R, Lehman TJ, Moorthy LN. Systemic arthritis in children: a review of clinical presentation and treatment. Int J Inflam. 2012;271569.
  2. Thomson W, Barrett JH, Donn R, Pepper L, Kennedy LJ, Ollier WER, et al. Juvenile idiopathic arthritis open link classified by the ILAR criteria: HLA associations in UK patients. Rheumatology. 2002;41(10):1183-1189.
  3. Ramanan AV, Grom AA. Does systemic-onset juvenile idiopathic arthritis belong under juvenile idiopathic arthritis? Rheumatology. 2005;44(11):1350–1353.
  4. Yokota S, Miyamae T, Imagawa T, Iwata N, Katakura S, Mori M. Inflammatory cytokines and systemic-onset juvenile idiopathic arthritis. Mod Rheumatol. 2004;14(1):12-17.
  5. Yokota S, Miyamae T, Imagawa T, Katakura S, Kurosawa R, Mori M. Clinical study of tocilizumab in children with systemic-onset juvenile idiopathic arthritis. Clin Rev Allergy Immunol. 2005;28(3):231-238.
  6. Behrens EM, Beukelman T, Gallo L, et al. Evaluation of the presentation of systemic onset juvenile rheumatoid arthritis: data from the Pennsylvania Systemic Onset Juvenile Arthritis Registry (PASOJAR). J Rheumatol. 2008;35(2):343–348.
  7. Berntson L, Andersson Gare B, Fasth A, et al. Incidence of juvenile idiopathic arthritis in the Nordic countries. A population based study with special reference to the validity of the ILAR and EULAR criteria. J Rheumatol. 2003;30:2275-2282.
  8. Varsani H, Patel A, van Kooyk Y, et al. Synovial dendritic cells in juvenile idiopathic arthritis (JIA) express receptor activator of NF-kappaB (RANK). Rheumatology (Oxford). 2003;42:583-590.
  9. Modesto C, Woo P, García-Consuegra J, et al. Systemic onset juvenile chronic arthritis, polyarticular pattern and hip involvement as markers for a bad prognosis,” Clin Exp Rheumatol. 2001;19:211-217.
  10. DeWitt EM, Kimura Y, Beukelman T, et al. Consensus Treatment Plans for New-Onset Systemic Juvenile Idiopathic Arthritis. Arthritis care & research. 2012;64(7):1001-1010.
  11. Barone P, Pignataro R, Garozzo MT, Leonardi S. IL-6 blockers in systemic onset juvenile idiopathic arthritis. Immunotherapy. 2016;8(1):79-87.

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Last updated: 2018-06-21 19:32